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| | <StructureSection load='6umi' size='340' side='right'caption='[[6umi]], [[Resolution|resolution]] 2.40Å' scene=''> | | <StructureSection load='6umi' size='340' side='right'caption='[[6umi]], [[Resolution|resolution]] 2.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6umi]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UMI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6UMI FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6umi]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UMI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6UMI FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6umg|6umg]], [[6umh|6umh]], [[6umj|6umj]]</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4Å</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6umi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6umi OCA], [http://pdbe.org/6umi PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6umi RCSB], [http://www.ebi.ac.uk/pdbsum/6umi PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6umi ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6umi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6umi OCA], [https://pdbe.org/6umi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6umi RCSB], [https://www.ebi.ac.uk/pdbsum/6umi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6umi ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
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| | </div> | | </div> |
| | <div class="pdbe-citations 6umi" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6umi" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Mohr, C]] | + | [[Category: Mohr C]] |
| - | [[Category: Fragment antigen binding]]
| + | |
| - | [[Category: Immune system]]
| + | |
| Structural highlights
Publication Abstract from PubMed
Calcitonin-gene-related peptide (CGRP) plays a key role in migraine pathophysiology. Aimovig (erenumab; erenumab-aooe in the United States) is the only US Food and Drug Administration (FDA)-approved monoclonal antibody (mAb) therapy against the CGRP receptor (CGRPR) for the prevention of migraine. Aimovig is also the first FDA-approved mAb against a G-protein-coupled receptor (GPCR). Here, we report the architecture and functional attributes of erenumab critical for its potent antagonism against CGRPR. The crystal structure of erenumab in complex with CGRPR reveals a direct ligand-blocking mechanism, enabled by a remarkable 21-residue-long complementary determining region (CDR)-H3 loop, which adopts a tyrosine-rich helix-turn tip and projects into the deep interface of the calcitonin receptor-like receptor (CLR) and RAMP1 subunits of CGRPR. Furthermore, erenumab engages with residues specific to CLR and RAMP1, providing the molecular basis for its exquisite selectivity. Such structural insights reveal the drug action mechanism of erenumab and shed light on developing antibody therapeutics targeting GPCRs.
Molecular Insight into Recognition of the CGRPR Complex by Migraine Prevention Therapy Aimovig (Erenumab).,Garces F, Mohr C, Zhang L, Huang CS, Chen Q, King C, Xu C, Wang Z Cell Rep. 2020 Feb 11;30(6):1714-1723.e6. doi: 10.1016/j.celrep.2020.01.029. PMID:32049005[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Garces F, Mohr C, Zhang L, Huang CS, Chen Q, King C, Xu C, Wang Z. Molecular Insight into Recognition of the CGRPR Complex by Migraine Prevention Therapy Aimovig (Erenumab). Cell Rep. 2020 Feb 11;30(6):1714-1723.e6. doi: 10.1016/j.celrep.2020.01.029. PMID:32049005 doi:http://dx.doi.org/10.1016/j.celrep.2020.01.029
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